Cyclic GMP has been implicated in the loss of growth control characteristic of the human leukemic state. Recently, I have found that inhibition of guanylate cyclase activity by addition of a crude inhibitor from the bitter melon (Momordica charantia abreviata) kills leukemic human lymphocytes but does not affect normal lymphocytes. This suggests that elevated cyclic GMP levels are a requirement for leukemic cell growth. Since we have found that all human lymphocytes lack significant cyclic GMP phosphodiesterase activity it is critically important to determine the mechanisms by which this nucleotide becomes and remains elevated in the leukemic cell. This could occur through elevated guanylate cyclase activity, through an impaired or inadequate elimination mechanism, or both. The questions to be addressed in this study are: How is the cyclic GMP level controlled in normal human lymphocytes, and, how is this control altered in leukemic cells? To answer these questions we will, 1) purify the bitter melon guanylate cyclase inhibitor and compare its effects on guanylate cyclase activity from leukemic and lectin-stimulated normal human lymphocytes. 2) determine the mechanisms by which cyclic GMP is eliminated from human lymphocytes, and 3) establish the rate of synthesis and elimination of cyclic GMP from leukemic and normal human lymphocytes. By this approach, we hope to characterize on a molecular level the reason for abnormal cyclic GMP levels in the leukemic state.